Eficácia e segurança dos anticorpos anti-amiloide na doença de Alzheimer inicial
revisão sistemática sobre Lecanemab e Donanemab
Palavras-chave:
Anticorpos monoclonais, Comprometimento cognitivo leve, Doença de Alzheimer, Peptídeos beta-Amiloides, Revisão sistemáticaResumo
A doença de Alzheimer tem sido historicamente tratada por fármacos sintomáticos, sem modificação consistente do curso biológico da enfermidade. A aprovação recente de anticorpos monoclonais anti-amiloide deslocou esse cenário, especialmente em pacientes com comprometimento cognitivo leve ou demência leve associados à patologia amiloide. Esta revisão sistemática, sem metanálise, analisou evidências sobre eficácia e segurança do lecanemab e do donanemab na doença de Alzheimer inicial. Foram incluídos ensaios clínicos randomizados, duplocegos e controlados por placebo que avaliaram esses fármacos em populações com confirmação biomarcadora de doença de Alzheimer. A síntese foi organizada conforme recomendações PRISMA 2020 e SWiM, agrupando os achados por fármaco, fase do estudo, desfechos cognitivo-funcionais, biomarcadores e eventos adversos. Quatro ensaios clínicos atenderam aos critérios de elegibilidade. Lecanemab e donanemab reduziram a carga amiloide e desaceleraram o declínio cognitivo-funcional em estudos de fase 3, embora com magnitude absoluta moderada. Os principais eventos adversos foram anormalidades de imagem relacionadas ao amiloide, reações infusionais e eventos hemorrágicos raros, com maior risco em portadores de ApoE ε4. Os achados indicam avanço terapêutico real, porém restrito a pacientes cuidadosamente selecionados, com necessidade de confirmação biomarcadora, ressonância magnética seriada e infraestrutura assistencial capaz de manejar eventos adversos.
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